Cannabinoid type 1 receptor availability imaging in attention-deficit/hyperactivity disorder using [18F]MK-9470 positron emission tomography: study protocol of the CB1-ADHD study.

Miederer I.; Schofer M.; Ruckes C.; Retz W.; Schreckenberger M.; Sebastian A. · EJNMMI reports · 2026

**Background & Methods** This is a prospective controlled study protocol investigating CB1 receptor availability in ADHD using [18F]MK-9470 PET imaging. The study will compare three groups (n=34 each): medication-naïve ADHD participants, methylphenidate-treated ADHD participants, and healthy controls. Primary outcome measures CB1 receptor distribution volume in the striatum, with secondary outcomes including CB1 availability in prefrontal cortex, plasma endocannabinoid concentrations (anandamide and 2-arachidonoylglycerol), and neuropsychological assessments of attention and impulsivity. **Key Findings** This is a study protocol document; no results are currently available. The study is designed to: • Evaluate CB1 receptor availability differences between medication-naïve ADHD patients, methylphenidate-treated patients, and healthy controls using selective radiotracer [18F]MK-9470 PET imaging • Correlate CB1 receptor distribution in fronto-striatal networks with behavioral measures of impulsivity and attention, based on the dual pathway model of ADHD pathophysiology • Measure peripheral endocannabinoid biomarkers alongside neuroimaging to establish potential mechanistic links between the endocannabinoid system and ADHD symptomatology **Dosage & Administration** Not reported. This is a study protocol document that does not detail specific cannabinoid dosing, as the investigation focuses on endogenous CB1 receptor availability rather than therapeutic cannabinoid administration. **Safety & Adverse Effects** Not reported. The protocol does not address safety or adverse effects, as this is a neuroimaging biomarker study rather than a therapeutic intervention trial. **Evidence Quality** This study protocol represents preliminary stage research with no completed data. As a controlled observational neuroimaging study, it will provide moderate-level evidence regarding CB1 receptor biology in ADHD. Key limitations include: modest sample size (102 total participants), cross-sectional design limiting causal inference, potential confounding from methylphenidate's neurobiological effects, and inability to directly test cannabinoid therapeutics. The study addresses an important gap in understanding endocannabinoid system involvement in ADHD pathogenesis and may inform future therapeutic development, but results require replication and validation before clinical implementation.

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